Allylic alcohols chiral hydroperoxide synthesis

Among the reactions catalyzed by titanium complexes, the asymmetric epoxidation of allylic alcohols developed by Sharpless and coworkers [752, 807-810] has found numerous synthetic applications. Epoxidation of allylic alcohols 3.16 by ferf-BuOOH under anhydrous conditions takes place with an excellent enantioselectivity (ee > 95%) when promoted by titanium complexes generated in situ from Ti(0/ -Pr)4 and a slight excess of diethyl or diisopropyl (R,R)- or (iS, 5)-tartrates 2.69. The chiral complex formed in this way can be used in stoichiometric or in catalytic amounts. For catalytic use, molecular sieves must be added. Because both (RJ )- and (5,5)-tartrates are available, it is posable to obtain either enantiomeric epoxide from a single allylic alcohol. Cumene hydroperoxide (PhCMe20OH) can also be used in place of ferf-BuOOH. This method has been applied to industrial synthesis of enantiomeric glycidols [811, 812]. 

Although it was also Henbest who reported as early as 1965 the first asymmetric epoxidation by using a chiral peracid, without doubt, one of the methods of enantioselective synthesis most frequently used in the past few years has been the "asymmetric epoxidation" reported in 1980 by K.B. Sharpless [3] which meets almost all the requirements for being an "ideal" reaction. That is to say, complete stereofacial selectivities are achieved under catalytic conditions and working at the multigram scale. The method, which is summarised in Fig. 10.1, involves the titanium (IV)-catalysed epoxidation of allylic alcohols in the presence of tartaric esters as chiral ligands. The reagents for this asyimnetric epoxidation of primary allylic alcohols are L-(+)- or D-(-)-diethyl (DET) or diisopropyl (DIPT) tartrate,27 titanium tetraisopropoxide and water free solutions of fert-butyl hydroperoxide. The natural and unnatural diethyl tartrates, as well as titanium tetraisopropoxide are commercially available, and the required water-free solution of tert-bnty hydroperoxide is easily prepared from the commercially available isooctane solutions. 

Chiral epoxides are important intermediates in organic synthesis. A benchmark classic in the area of asymmetric catalytic oxidation is the Sharpless epoxidation of allylic alcohols in which a complex of titanium and tartrate salt is the active catalyst [273]. Its success is due to its ease of execution and the ready availability of reagents. A wide variety of primary allylic alcohols are epoxidized in >90% optical yield and 70-90% chemical yield using tert-butyl hydroperoxide as the oxygen donor and titanium-isopropoxide-diethyltartrate (DET) as the catalyst (Fig. 4.97). In order for this reaction to be catalytic, the exclusion of water is absolutely essential. This is achieved by adding 3 A or 4 A molecular sieves. The catalytic cycle is identical to that for titanium epoxidations discussed above (see Fig. 4.20) and the actual catalytic species is believed to be a 2 2 titanium(IV) tartrate dimer (see Fig. 4.98). The key step is the preferential transfer of oxygen from a coordinated alkylperoxo moiety to one enantioface of a coordinated allylic alcohol. For further information the reader is referred to the many reviews that have been written on this reaction [274, 275]. 

Sharpless asymmetric epoxidation ° is an enantioselective epoxidation of an allylic alcohol with ferf-butyl hydroperoxide (f-BuOOH), titanium tetraisopropoxide [Ti(0-fPr)4] and (-b)- or (—)-diethyl tartrate [(-b)- or (—)-DET] to produce optically active epoxide from achiral allylic alcohol. The reaction is diastereoselective for a-substituted allylic alcohols. Formation of chiral epoxides is an important step in the synthesis of natural products because epoxides can be easily converted into diols and ethers. 

The classical method for the synthesis of epoxy alcohols is the epoxidation of allylic alcohols, the latter accessible by reduction of allylic hydroperoxides or other more traditional methods. One of the most valuable reactions for preparative purposes is the Sharpless method82 83, in which, for chiral allylic alcohols, the epoxy alcohols are produced diastereoselectively and, in the presence of chiral ligands, also in high enantioselectivity (see Section D.4.5.1.). 

A general synthesis for all diastereomeric L-hexoses, as an example for monosaccharides that often do not occur in the chiral pool, has been worked out. The epoxidation of allylic alcohols with tertiary butyl hydroperoxide in presence of titanyl tartaric ester catalysts converts the carbon-carbon double bond stereose-lectively to a diol and is thus ideally suited for the preparation of carbohydrates. The procedure is particularly useful as a repetitive two-carbon homologiza-tion in total syntheses of higher monosaccharides and other poly hydroxy compounds. It starts with a Wittig reaction of a benzylated a-hydroxy aldehyde with (triphenylphosphoran-ylidene)acetaldehyde to produce the olefinic double bond needed for epoxidation. Reduction with sodium-borohydride... 

Of particular value in complex syntheses is a technique for epoxidation that can be applied to allylic alcohols and that directs the approach of the oxidizing group to one or the other of the two faces of the double bond. This results in the formation of one enantiomeric form in excess of the other and, thus, stands as an asymmetric synthesis. The technique is simple and consists of the formation of a chiral catalyst, a coordination complex, from titanium tetra-isopropoxide and one of the optically active forms of a dialkyl tartrate. The allylic alcohol associates with this complex in a specific way and then is epoxidized on one face by t-butyl hydroperoxide. The epoxide is produced in high enantiomeric excess, frequently more than 95%. This process has been used widely in organic synthesis since its discovery in 1980. It is now known as the Sharpless epoxidation. 

In 1980, K. B. Sharpless (then at the Massachusetts Institute of Technology, presently at The Scripps Research Institute) and co-workers reported a method that has since become one of the most valuable tools for chiral synthesis. The Sharpless asymmetric epoxidation is a method for converting allylic alcohols (Section 11.1) to chiral epoxy alcohols with very high enan-tioselectivity (i.e., with preference for one enantiomer rather than formation of a racemic mixture). In recognition of this and other work in asymmetric oxidation methods (see Section 8.16A), Sharpless received half of the 2001 Nobel Prize in Chemistry (the other half was awarded to W. S. Knowles and R. Noyori see Section 7.14). The Sharpless asymmetric epoxidation involves treating the allylic alcohol with tert-butyl hydroperoxide, titanium(IV) tetraisopropoxide [Ti(0—/-POJ, and a specific stereoisomer of a tartrate ester. (The tartrate stereoisomer that is chosen depends on the specific enantiomer of the epoxide desired). The following is an example ... 

Sharpless epoxidation (Chapter 14 Lagniappe) A method for enantioselective synthesis of a chiral epoxide by treatment of an allylic alcohol with ferf-butyl hydroperoxide, (CHa)3C—OOH, in the presence of titanium tetraisopropoxide and diethyl tartrate. 

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